Considerable variation exists among inbred strains of mice in their behavior toward bitter-tasting compounds. These differences have been demonstrated almost exclusively using long-term (24- or 48-hour) intake tests. Such natural variation in behavior has fostered physiological, biochemical, and molecular research aimed at elucidating taste transduction events and the identity of genes underlying the mechanisms of bitter taste. Two inbred strains exist that differ substantially in their intake of bitter stimuli: SWR/J (SW: bitter sensitive) and C3HeB/FeJ (C3: bitter insensitive). An understanding of how these strains differ physiologically could provide information useful for developing models of bitter taste function. However, very little is known about the responsiveness of taste receptor cells of these strains to bitter stimuli. Further, it is not certain that the long- term intake tests used to contrast these strains provide uncontaminated indicators of gustatory function. The approach taken in this application is to combine refined behavioral procedures with electrophysiological studies of taste receptor cells to elucidate the physiological bases of these behavioral differences. Behavioral measures from mice from both strains will be acquired using a short-term test designed to minimize non-taste (e.g., post-ingestive) factors. Precise concentration-response functions acquired in this way will provide a clear indication of the behavioral differences among bitter stimuli for these strains, based on taste cues. In electrophysiological experiments, taste receptor cells from the tongue and palate of these mice will be investigated using whole-cell-recording methods in an intact epithelial preparation. Cells will be tested with an array of bitter stimuli to test the hypothesis that the behavioral differences between strains are due to: 1) a greater number of cells responding to bitter stimuli in the bitter-sensitive SW strain; or 2) an altered concentration-response function for bitter stimuli in the bitter-insensitive C3 strain. By examining these strain differences in receptor cell function, these studies should help to link ongoing molecular advances to the neural mechanisms underlying bitter taste function.